Living related versus deceased donor liver transplantation for maple syrup urine disease

• Published in: Molecular genetics and metabolism 2016-03, Vol.117 (3), p.336-343
• Main Authors: Feier, Flavia, Schwartz, Ida Vanessa D., Benkert, Abigail R., Neto, Joao Seda, Miura, Irene, Chapchap, Paulo, da Fonseca, Eduardo Antunes, Vieira, Sandra, Zanotelli, Maria Lúcia, Vairo, Filippo Pinto e, Camelo, Jose Simon, Margutti, Ana Vitoria Barban, Mazariegos, George V., Puffenberger, Erik G., Strauss, Kevin A.
• Format: Article
• Language: English
• Subjects: 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) - blood; 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) - genetics; 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) - metabolism; Adult; Branched chain ketoacid dehydrogenase; Brazil; Child; Child, Preschool; Diet; Domino transplantation; Female; Follow-Up Studies; Heterozygote; Humans; Isoleucine - blood; Leucine - blood; Liver Transplantation; Living Donors; Living related donor liver transplantation; Male; Maple syrup urine disease; Maple Syrup Urine Disease - genetics; Maple Syrup Urine Disease - physiopathology; Maple Syrup Urine Disease - surgery; Maple Syrup Urine Disease - therapy; Oxidation-Reduction; Sequence Analysis, DNA; Tissue Donors; Treatment Outcome; Valine - blood
• ISSN: 1096-7192; 1096-7206
• DOI: 10.1016/j.ymgme.2016.01.005

Maple syrup urine disease (MSUD) is an inherited disorder of branched chain ketoacid (BCKA) oxidation associated with episodic and chronic brain disease. Transplantation of liver from an unrelated deceased donor restores 9–13% whole-body BCKA oxidation capacity and stabilizes MSUD. Recent reports document encouraging short-term outcomes for MSUD patients who received a liver segment from mutation heterozygous living related donors (LRDT). To investigate effects of living related versus deceased unrelated grafts, we studied four Brazilian MSUD patients treated with LRDT who were followed for a mean 19±12 postoperative months, and compared metabolic and clinical outcomes to 37 classical MSUD patients treated with deceased donor transplant. Patient and graft survival for LRDT were 100%. Three of 4 MSUD livers were successfully domino transplanted into non-MSUD subjects. Following LRDT, all subjects resumed a protein-unrestricted diet as mean plasma leucine decreased from 224±306μM to 143±44μM and allo-isoleucine decreased 91%. We observed no episodes of hyperleucinemia during 80 aggregate postoperative patient-months. Mean plasma leucine:isoleucine:valine concentration ratios were ~2:1:4 after deceased donor transplant compared to ~1:1:1.5 following LRDT, resulting in differences of predicted cerebral amino acid uptake. Mutant heterozygous liver segments effectively maintain steady-state BCAA and BCKA homeostasis on an unrestricted diet and during most catabolic states, but might have different metabolic effects than grafts from unrelated deceased donors. Neither living related nor deceased donor transplant affords complete protection from metabolic intoxication, but both strategies represent viable alternatives to nutritional management. •Transplantation of a liver segment from a mutation heterozygous living donor effectively controls classical maple syrup urine disease (MSUD).•Living related versus deceased donor transplants for MSUD result in similar but not identical metabolic outcomes.•Live donor liver transplantation for MSUD improves access to effective treatment in resource-limited clinical settings.•Through the domino procedure, live donor transplant adds a new liver to the donor pool.